肾移植患者免疫抑制治疗的群体药代动力学研究

Title:Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients

Volume: 23 Issue: 19

Author(s): Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic, Iztok Grabnar

Affiliation:

关键词: 环孢素、他克莫司、雷帕霉素，霉酚酸，变异性，药代动力学因素，肾移植患者，人口模型。

摘要: Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.

Cite this article as:

Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic, Iztok Grabnar , Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients, Current Medicinal Chemistry 2016; 23 (19) . https://dx.doi.org/10.2174/0929867323666151221150214